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To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Poly (methyl methacrylate)/hydroxyapatite (PMMA/HAp) nanocomposites with HAp nanoparticles content of 12 wt.% were obtained by free-radical polymerization synthesis. Three different concentrations of benzoyl peroxide (PBO) of 3, 6, and 12 wt.% were studied. The results showed that the concentration of PBO has an effect on the performance of composites. In particular, the nanocomposite with the highest concentration of PBO presented the best mechanical and tribological behavior, as well as the lowest values of water absorption and porosity percent.
The aim of this research was to investigate the influence of substrate roughness on the adhesion and tribological performance of thin TiN coatings obtained by physical vapor deposition. For that purpose, substrates of AISI H13 steel with surface finishes of 0.06, 0.28 and 0.90 μm in Ra were coated with TiN under the same coating conditions. The chemical composition of the steel, as well as that of the TiN coating, were obtained using EDS analysis. Adhesion tests were carried out following the procedure of BSi 1071-8 standard while hardness was evaluated by ASTM C 1327-03. On the other hand, dry sliding friction tests were conducted with a pin-on-disk tribometer, according to the ASTM G 99-05 standard. This study showed that the roughness of the coating increases as the substrate roughness increases. Regarding adhesion and hardness, all the samples showed an adhesion class 1 according to the standard and a hardness value of 14.51 GPa. Nevertheless, the highest substrate roughness produced the best adhesion. On the other hand, the lowest values for the friction coefficient and wear behavior were obtained by the sample with the lowest substrate roughness of 0.06 µm. In addition, it was found that friction and wear increase when the substrate roughness increases.
Robert Nozick allegedly introduced his liberal theory of private ownership as an objection to theories of end-state justice. Nevertheless, we show that, in a stylized framework for the allocation of goods in joint ventures, both approaches can be seen as complementary. More precisely, in such a context, self-ownership (the basis for Nozick’s entitlement theory of justice) followed by voluntary transfer (Nozick’s principle of just transfer) can lead to end-state fairness (as well as Pareto efficiency). Furthermore, under a certain solidarity condition, the only way to achieve end-state fairness, following Nozick’s procedure, is to endorse an egalitarian rule for the initial assignment of rights.
The temporal correlation between neutron and hard X-ray (HXR) emissions from a hundred joules plasma focus device (PF-400J) was studied. A method, time history analysis, to estimate the time of origin of neutrons with respect to HXRs is applied. In most of the discharges, it was found that neutrons are originated before HXRs in the axial direction and after HXRs in the radial direction. In some discharges, the time difference between HXRs and neutrons origin was found large enough, so that it can be interpreted that those neutrons would have been originated before the pinch. A qualitative discussion is conjectured to explain the experimental observations.
Throughout its range in Latin America the jaguar Panthera onca is threatened by habitat loss and fragmentation, and conflict with humans. Protected areas in Panama harbour some of the last remaining suitable habitat for jaguars and are vital to conservation. However, no previous studies had assessed which factors in particular affect the tolerance of rural Panamanians towards jaguars and National Park conservation, which is important to jaguar persistence. Whether these factors are consistent with previous research on human–carnivore coexistence is unclear. To address this we estimated the number of instances of depredation of cattle by jaguars, and assessed attitudes and perceptions of rural Panamanians. We conducted semi-structured interviews in two disparate study areas: Cerro Hoya National Park and Darién National Park. Depredation events were more frequent in the latter, but only residents of the former reported conflict between people and coyotes Canis latrans. Positive perceptions of jaguars and National Parks, and criticism of park management, increased with level of education and land ownership. Men were more open to receiving help on their farms to mitigate impacts of jaguars, and more tolerant of the presence of jaguars, than women. Residents from both study areas indicated high appreciation for their respective National Parks. We provide recommendations to improve community outreach and education initiatives, and suggest priority areas for future mitigation efforts concerning human–jaguar interactions in Panama.
Little is known about Salmonella serovars circulating in backyard poultry and swine populations worldwide. Backyard production systems (BPS) that raise swine and/or poultry are distributed across Chile, but are more heavily concentrated in central Chile, where industrialized systems are in close contact with BPS. This study aims to detect and identify circulating Salmonella serovars in poultry and swine raised in BPS. Bacteriological Salmonella isolation was carried out for 1744 samples collected from 329 BPS in central Chile. Faecal samples were taken from swine, poultry, geese, ducks, turkeys and peacocks, as well as environmental faecal samples. Confirmation of Salmonella spp. was performed using invA-polymerase chain reaction (PCR). Identification of serovars was carried out using a molecular serotyping approach, where serogroups were confirmed by a multiplex PCR of Salmonella serogroup genes for five Salmonella O antigens (i.e., D, B, C1, C2-C3, and E1), along with two PCR amplifications, followed by sequencing of fliC and fljB genes. A total of 25 samples (1·4% of total samples) from 15 BPS (4·6 % of total sampled BPS) were found positive for Salmonella. Positive samples were found in poultry (chickens and ducks), swine and environmental sources. Molecular prediction of serovars on Salmonella isolated showed 52·0% of S. Typhimurium, 16·0% of S. Infantis, 16·0% S. Enteritidis, 8·0% S. Hadar, 4·0% S. Tennessee and 4·0% S. Kentucky. Poor biosecurity measures were found on sampled BPS, where a high percentage of mixed confinement systems (72·8%); and almost half of the sampled BPS with improper management of infected mortalities (e.g. selling the carcasses of infected animals for consumption). Number of birds other than chickens (P = 0·014; OR = 1·04; IC (95%) = 1·01–1·07), mixed productive objective (P = 0·030; OR = 5·35; IC (95%) = 1·24–27·59) and mixed animal replacement origin (P = 0017; OR = 5·19; IC (95%) = 1·35–20·47) were detected as risk factors for BPS positivity to Salmonella spp. This is the first evidence of serovars of Salmonella spp. circulating in BPS from central Chile. Detected serovars have been linked to human and animal clinical outbreaks worldwide and in Chile, highlighting the importance of BPS on the control and dissemination of Salmonella serovars potentially hazardous to public health.
The upconversion nanoparticles (UCNPs) possess the ability to absorb near infrared energy (980 nm) and upconvert it to emit in the visible spectra. In this research, the UNCPs emit in red (660 nm) due to the electronic transitions between two rare earth ions: Er3+ and Yb3+, this process is called energy transfer upconversion (ETU). The UCNPs were functionalized with aminosilanes and folic acid receptors (UCNP-FR) and analyzed by transmission electron microscopy, Fourier transform infrared spectroscopy and luminescence measurements. UCNPs-FR of Y2O3 have a particle size of 70 ± 10 nm and the Gd2O3 have a 50 ± 10 nm particle size. Both showed a good luminescence spectrum in comparison with the bare ones. Cytotoxicity of different amounts between 0.001 µg/ml to 1 µg/ml of bare and functionalized UCNPs was measured with the colorimetric assay MTT in three cancer cell lines: human cervical adenocarcinoma (HeLa), human breast cancer cells MB-MDA-231. Some concentrations of bare UCNPs were cytotoxic for cancer cells; however after their functionalization they resulted to be non-cytotoxic. The functionalized UCNPs were able to bind to folate receptors which are overexpressed in cervical and breast cancers cells. It was demonstrated by confocal microscopy, that the functionalized UCNPs were internalized into the cancer cells, confirming that they can be used as biolabels for breast and cervical cancer cells.
The appropriate supply of nutrients in pregnant cows has been associated with the optimal development of foetal tissues, performance of their progeny and their meat quality. The aim of this study was to evaluate supplementation effects of grazing cows in different stages of gestation on skeletal muscle development and performance of the progeny. Thereby, 27 Nellore cows were divided into three groups (n=9 for each group) and their progeny as follows: UNS, unsupplemented during gestation; MID, supplemented from 30 to 180 days of gestation; LATE, supplemented from 181 to 281 days of gestation. The percentage composition of the supplement provided for the matrices was the following: ground corn (26.25%), wheat bran (26.25%) and soya bean meal (47.5%). The supplement was formulated to contain 30% CP. Supplemented matrices received 150 kg of supplement (1 and 1.5 kg/day for cows in the MID and LATE groups, respectively). After birth, a biopsy was performed to obtain samples of skeletal muscle tissue from calves to determine number and size of muscle fibres and for messenger RNA (mRNA) expression analysis. The percentage composition of the supplement provided for the progeny was the following: ground corn grain (30%), wheat bran (30%), soya bean meal (35%) and molasses (5%). The supplement was formulated to contain 25% CP and offered in an amount of 6 g/kg BW. Performance of the progeny was monitored throughout the suckling period. Means were submitted to ANOVA and regression, and UNS, MID and LATE periods of supplementation were compared. Differences were considered at P<0.10. Birth weight, average daily gain and weaning weight of the offspring did not differ among treatments (P>0.10). Similarly, no differences were observed between calves for nutrient intake (P>0.10). However, greater subcutaneous fat thickness (P=0.006) was observed in the calves of LATE group. The ribeye area (P=0.077) was greater in calves born from supplemented compared with UNS cows. The supplementation of pregnant cows did not affect the muscle fibre size of their progeny (P=0.208). On the other hand, calves born from dams supplemented at mid-gestation had greater muscle fibre number (P=0.093) compared with calves from UNS group. Greater mRNA expression of peroxysome proliferator-activated receptor α (P=0.073) and fibroblast growth factor 2 (P=0.003) was observed in the calves born from MID cows. Although strategic supplementation did not affect the BW of offspring, it did cause changes in carcass traits, number of myofibres, and mRNA expression of a muscle hypertrophy and lipid oxidation markers in skeletal muscle of the offspring.
Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions.
Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored.
Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = −0.28, p = 0.041) and left posterior (r = −0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of ‘autistic-like’ symptoms (r = −0.30, p = 0.028).
The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.
Traditionally, islands have been used as ecological and biogeographical models because of their assumed ecological simplicity, reduced ecosystem size and isolation. The vast number of Earth's oceanic islands play a key role in maintaining global biodiversity and serve as a rich source of evolutionary novelty. Research into the factors determining diversity patterns on islands must disentangle natural phenomena from anthropogenic causes of habitat transformation, interruption and enhancement of biological fluxes and species losses and gains in these geographically and ecologically limited environments. The anthropogenic ecological forcing of communication through global transport has profound implications regarding island–continent links. Anthropogenic disturbances along continental margins and insular coasts contribute to shaping island biotas in ecological time, but also have evolutionary consequences of global resonance. Patterns of human landscape and resource use (geographical space and ecological communities and species), as well as increasing ecological connectivity of oceanic islands and mainland, are chief driving forces in island biogeography that should be reappraised. Global indirect effects of human activities (i.e. climate change) may also affect islands and interact with these processes. We review the implications of direct and indirect anthropogenic disturbances on island biotic patterns, focusing on island size, isolation and introduced exotic species, as well as the unsettled issue of oceanic island ecological vulnerability.
Investigating whether high-risk human papillomavirus (HR-HPV) types tend to become grouped in a particular way and whether factors are associated with such grouping is important for measuring the real impact of vaccination. In total, 219 women proving positive for HPV as detected by real-time PCR were included in the study. Each sample was analysed for detecting and quantifying six viral types and the hydroxymethylbilane synthase gene. Multiple correspondence analysis led to determining grouping patterns for six HR-HPV types and simultaneous association with multiple variables and whether viral load was related to the coexistence of other viral types. Two grouping profiles were identified: the first included HPV-16 and HPV-45 and the second profile was represented by HPV-31, HPV-33 and HPV-58. Variables such as origin, contraceptive method, births and pregnancies, educational level, healthcare affiliation regime, atypical squamous cells of undetermined significance and viral load were associated with these grouping profiles. Different socio-demographic characteristics were found when coinfection occurred by phylogenetically related HPV types and when coinfection was due to non-related types. Biological characteristics, the number of viral copies, temporality regarding acquiring infection and competition between viral types could influence the configuration of grouping patterns. Characteristics related to women and HPV, influence such interactions between coexisting HPV types reflecting the importance of their evaluation.
This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
The present study employs a linear global stability analysis to investigate buoyancy-induced flickering of axisymmetric laminar jet diffusion flames as a hydrodynamic global mode. The instability-driving interactions of the buoyancy force with the density differences induced by the chemical heat release are described in the infinitely fast reaction limit for unity Lewis numbers of the reactants. The analysis determines the critical conditions at the onset of the linear global instability as well as the Strouhal number of the associated oscillations in terms of the governing parameters of the problem. Marginal instability boundaries are delineated in the Froude number/Reynolds number plane for different fuel jet dilutions. The results of the global stability analysis are compared with direct numerical simulations of time-dependent axisymmetric jet flames and also with results of a local spatio-temporal stability analysis.
Agroecology uses ecological processes and local resources rather than chemical inputs to develop productive and resilient livestock and crop production systems. In this context, breeding innovations are necessary to obtain animals that are both productive and adapted to a broad range of local contexts and diversity of systems. Breeding strategies to promote agroecological systems are similar for different animal species. However, current practices differ regarding the breeding of ruminants, pigs and poultry. Ruminant breeding is still an open system where farmers continue to choose their own breeds and strategies. Conversely, pig and poultry breeding is more or less the exclusive domain of international breeding companies which supply farmers with hybrid animals. Innovations in breeding strategies must therefore be adapted to the different species. In developed countries, reorienting current breeding programmes seems to be more effective than developing programmes dedicated to agroecological systems that will struggle to be really effective because of the small size of the populations currently concerned by such systems. Particular attention needs to be paid to determining the respective usefulness of cross-breeding v. straight breeding strategies of well-adapted local breeds. While cross-breeding may offer some immediate benefits in terms of improving certain traits that enable the animals to adapt well to local environmental conditions, it may be difficult to sustain these benefits in the longer term and could also induce an important loss of genetic diversity if the initial pure-bred populations are no longer produced. As well as supporting the value of within-breed diversity, we must preserve between-breed diversity in order to maintain numerous options for adaptation to a variety of production environments and contexts. This may involve specific public policies to maintain and characterize local breeds (in terms of both phenotypes and genotypes), which could be used more effectively if they benefited from the scientific and technical resources currently available for more common breeds. Last but not least, public policies need to enable improved information concerning the genetic resources and breeding tools available for the agroecological management of livestock production systems, and facilitate its assimilation by farmers and farm technicians.
Agroecology uses natural processes and local resources rather than chemical inputs to ensure production while limiting the environmental footprint of livestock and crop production systems. Selecting to achieve a maximization of target production criteria has long proved detrimental to fitness traits. However, since the 1990s, developments in animal breeding have also focussed on animal robustness by balancing production and functional traits within overall breeding goals. We discuss here how an agroecological perspective should further shift breeding goals towards functional traits rather than production traits. Breeding for robustness aims to promote individual adaptive capacities by considering diverse selection criteria which include reproduction, animal health and welfare, and adaptation to rough feed resources, a warm climate or fluctuating environmental conditions. It requires the consideration of genotype×environment interactions in the prediction of breeding values. Animal performance must be evaluated in low-input systems in order to select those animals that are adapted to limiting conditions, including feed and water availability, climate variations and diseases. Finally, we argue that there is no single agroecological animal type, but animals with a variety of profiles that can meet the expectations of agroecology. The standardization of both animals and breeding conditions indeed appears contradictory to the agroecological paradigm that calls for an adaptation of animals to local opportunities and constraints in weakly artificialized systems tied to their physical environment.
Y2O3 and Gd2O3 upconversion nanoparticles (UCN) co-doped with Yb3+ and Er3+ can absorb and upconvert near infrared (NIR) radiation into visible light. These UCN find application in bioimaging, as an important tool to diagnose and visualize cancer cells. The UCN can be used as biolabels to identify the cells; the nanoparticles can be coated and functionalized with ligands that bind to receptors on the surface of the cell. In this project, the UCN were synthesized by sol-gel method and subsequently coated with a thin silica shell by using the Stöber method. The core-shell UCN were functionalized with amine group to enable folic acid conjugation. The functionalized core-shell nanoparticles were analyzed by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and luminescence measurements. Concentrations of bare and coated/functionalized UCN between 0.001 µg/mL and 1 µg/mL were tested on two different cell lines from human cervix carcinoma (HeLa) and human colorectal adenocarcinoma (DLD-)1 with colorimetric assay based on the MTT reagent (methy-134 thiazolyltetrazolium). The results show good luminescence spectra on all core-shell UCN. The MTT assays show that some concentrations of bare UCN of Y2O3: Er, Yb (1%, 1% mol) and Gd2O3 were cytotoxic for cervical adenocarcinoma cells (HeLa). For human colorectal adenocarcinoma all UCN are non-cytotoxic. The UCN with silica-aminosilane functionalization (APTS/TEOS) were non-cytotoxic on both cell lines.
RNA polymerase III (Pol III) synthesizes small RNA molecules that are essential for cell viability. Accurate initiation of transcription by Pol III requires general transcription factor TFIIIB, which is composed of three subunits: TFIIB-related factor BRF1, TATA-binding protein and BDP1. Here we report the molecular characterization of BRF1 in Trypanosoma brucei (TbBRF1), a parasitic protozoa that shows distinctive transcription characteristics. In silico analysis allowed the detection in TbBRF1 of the three conserved domains located in the N-terminal region of all BRF1 orthologues, namely a zinc ribbon motif and two cyclin repeats. Homology modelling suggested that, similarly to other BRF1 and TFIIB proteins, the TbBRF1 cyclin repeats show the characteristic structure of five α-helices per repeat, connected by a short random-coiled linker. As expected for a transcription factor, TbBRF1 was localized in the nucleus. Knock-down of TbBRF1 by RNA interference (RNAi) showed that this protein is essential for the viability of procyclic forms of T. brucei, since ablation of TbBRF1 led to growth arrest of the parasites. Nuclear run-on and quantitative real-time PCR analyses demonstrated that transcription of all the Pol III-dependent genes analysed was reduced, at different levels, after RNAi induction.